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      Teaching an old dog new tricks: reactivated developmental signaling pathways regulate ABCB1 and chemoresistance in cancer

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          Abstract

          Oncogenic multidrug resistance (MDR) is a multifactorial phenotype intimately linked to deregulated expression of detoxification transporters. Drug efflux transporters, particularly the MDR P-glycoprotein ABCB1, represent a central mechanism by which not only chemotherapeutic drugs are extruded or sequestered to prevent drug delivery to their intracellular targets, but also for inhibiting apoptotic cell death cues, such as removal of proapoptotic signals. Several cell populations exhibiting the MDR phenotype co-exist within a tumor, such as cells forming the bulk tumor cell mass, cancer stem cells, and cancer persister cells. The key to regulation of ABCB1 expression is the cellular transcriptional machinery. Developmental signaling pathways (e.g, Hedgehog, Notch, Wnt/β-catenin, TGFβ, PITX2) are pivotal in governing cell proliferation, survival, differentiation and guiding cell migration during embryogenesis, and their reactivation during carcinogenesis, which is of particular significance for tumor initiation, progression, and metastasis, also leads to the upregulation of ABCB1. These pathways also drive and maintain cancer cell stemness, for which ABCB1 is used as a marker. In this review, the contribution of canonical and non-canonical developmental signaling pathways in transcriptional regulation of ABCB1 to confer MDR in cancer is delineated.

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          The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
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            The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.

            The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access resource for interactive exploration of multidimensional cancer genomics data sets, currently providing access to data from more than 5,000 tumor samples from 20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications. © 2012 AACR.
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              Immunity, inflammation, and cancer.

              Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Inflammation also affects immune surveillance and responses to therapy. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. This review outlines the principal mechanisms that govern the effects of inflammation and immunity on tumor development and discusses attractive new targets for cancer therapy and prevention. 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Cancer Drug Resist
                Cancer Drug Resist
                Cancer Drug Resistance
                OAE Publishing Inc.
                2578-532X
                2021
                19 June 2021
                : 4
                : 2
                : 424-452
                Affiliations
                Institute for Physiology, Pathophysiology and Toxicology, ZBAF, Witten/Herdecke University , Witten 58453, Germany.
                Author notes
                Correspondence Address: Prof. Wing-Kee Lee, Institute for Physiology, Pathophysiology and Toxicology, Witten/Herdecke University, Stockumer Strasse 12, Witten 58453, Germany. E-mail: wing-kee.lee@ 123456uni-wh.de

                Academic Editor: Godefridus J. Peters | Copy Editor: Yue-Yue Zhang | Production Editor: Yue-Yue Zhang

                Article
                10.20517/cdr.2020.114
                9019277
                35582031
                0d69c479-95a7-43ba-93da-49ef033292fd
                © The Author(s) 2021.

                © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 11 December 2020
                : 06 February 2021
                : 20 February 2021
                Funding
                Funded by: the Intramural Research Program at Witten/Herdecke University and Westmann-Westerdorp Foundation
                Funded by: DFG (German Research Foundation) Grants TH345 and the Centre for Biomedical Education and Research (ZBAF) at Witten/Herdecke University
                Categories
                Review

                drug resistance,abc transporters,transforming growth factor beta,tumor heterogeneity,tumor cell biology

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